PB2357: TRIAL IN PROGRESS: OUTCOMES IN PATIENTS WITH RELAPSED/REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA TREATED WITH SYSTEMIC THERAPY FROM REAL-WORLD EXPERIENCE (ORCHID)
Authors: Catherine Thieblemont, Qiufei MA, Christian Hampp, James Harnett, Rachel E Sobel, Jessica J Jalbert, Ruben Gw Quek, Wenhui Wei, Ning Wu, Vera Mastey, Joy Wang, Anit Bajwa, Benedikt Maissenhaelter, Chantal van Gils, Shivani Aggarwal, Aafia Chaudhry, Hesham Mohamed, Srikanth Ambati, Emmanuel Bachy, Gandhi Laurent Damaj
Journal: HemaSphere (2023)

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Diffuse large B-cell lymphoma (DLBCL) accounts for around one-third of all newly diagnosed non-Hodgkin lymphomas and 20–50% of patients will relapse or be refractory (R/R) to induction treatment. New treatments have significantly improved outcomes for patients in the third-line setting and beyond (≥3L). Large-scale, patient-level, real-world (RW) evidence studies can provide a good understanding of outcomes with currently available therapies in routine clinical practice and contextualize results from uncontrolled, single arm clinical trials. Aims: The ORCHID study aims to characterize RW treatment patterns and outcomes in a large cohort of ~700 patients with R/R DLBCL initiating ≥3L systemic therapy from over 30 clinical sites in 12 countries across North America, Europe, and Asia. Among them, an analytic cohort will be created of ~300 patients who have measurable disease at baseline and PET/CT scans during follow-up, unless they died. Methods: ORCHID (NCT05338892) is an electronic medical record-based observational, retrospective cohort study of patients with R/R DLBCL who have received ≥2 prior lines of systemic therapy, including an anti-CD20 antibody and an alkylator. The study population will be selected based on similar eligibility criteria as the R/R DLBCL arm of the odronextamab ELM-2 trial (NCT03888105; Figure). Patients must have measurable disease and have initiated ≥1 additional line of systemic therapy (salvage therapy) between Jan 01, 2015 and Jun 30, 2021 (indexing period) after meeting the criteria for R/R DLBCL. ORCHID is designed to contextualize outcomes from patients with R/R DLBCL enrolled in contemporaneous single-arm studies. To estimate RW objective response rate (ORR) by independent central review (ICR), analytical cohorts will be created from the ORCHID population based on data requirements and matching feasibility. Patients will be propensity score matched and/or weighted to each patient in the ELM-2 trial (anticipated cohort, n=127). To identify prognostic variables for inclusion in the propensity score model, a systematic literature review was conducted (PROSPERO CRD42022307557) and findings were ranked by three key opinion leaders. The most important prognostic variables identified included early chemoimmunotherapy failure, Eastern Cooperative Oncology Group performance status, refractory to last line of therapy, number of prior treatment lines, double or triple-hit lymphoma, age, International Prognostic Index, Ann Arbor stage, and lactate dehydrogenase. Results: The primary endpoint of ORCHID is ICR-assessed ORR (Lugano classification). Secondary outcomes include physician-assessed ORR as well as complete response rate, progression-free survival, duration of response, and disease control rate assessed by ICR and treating physician. Overall survival and time to next treatment will also be evaluated. Subgroups of interest will include historical (Jan 01, 2015 to Nov 12, 2019) versus contemporary treatment (Nov 13, 2019 to Jun 30, 2021), chimeric antigen receptor (CAR)-T cell therapy versus other salvage regimens, and geographic region. Sensitivity analyses will be conducted in expanded cohorts to assess the impact of eligibility criteria and availability of scans. Summary/Conclusion: When complete, ORCHID will provide important current information on the RW outcomes of patients with DLBCL and provide a valuable source of control data for comparative studies in R/R DLBCL.Keywords: Non-Hodgkin’s lymphoma, Relapsed lymphoma, Diffuse large B cell lymphoma, Real world data